Use of inhibitors of the renin angiotensin system and COVID-19 prognosis: a systematic review and meta-analysis

  1. Jessica Barochiner
  2. Rocio Martinez

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Abstract

Background: controversy has arisen in the scientific community on whether the use of renin angiotensin system (RAS) inhibitors in the context of COVID-19 would be of benefit or harmful. A meta-analysis of eligible studies comparing the occurrence of severe and fatal COVID-19 in infected patients who were under treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) vs no treatment or other antihypertensives was conducted. Methods: PubMed, Google Scholar, the Cochrane Library, MedRxiv and BioRxiv were searched for relevant studies. Fixed-effect models or random-effect models were used depending on the heterogeneity between estimates. Results: a total of fifteen studies with 21,614 patients were included. The use of RAS inhibitors was associated with a non-significant 20% decreased risk of the composite outcome (death, admission to intensive care unit, mechanical ventilation requirement or progression to severe or critical pneumonia): RR 0.81 (95%CI: 0.63-1.04), p=0.10, I2=82%. In a subgroup analysis that included hypertensive subjects only, ACEI/ARB were associated with a 27% significant decrease in the risk of the composite outcome (RR 0.73 (95%CI: 0.56-0.96), p=0.02, I2=65%). Conclusion: the results of this pooled analysis suggest that the use of ACEI/ARB does not worsen the prognosis, and could even be protective in hypertensive subjects. Patients should continue these drugs during their COVID-19 illness.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.19.20106799: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationThe following search strategy was implemented: Articles were limited to human studies, original articles including comparative studies, both randomized controlled trials (RCTs) or non-RCTs where treatment with ACEI and/or ARB was compared with no treatment or other antihypertensive drugs in terms of COVID-19 infection serious adverse outcomes.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableAlso, total population, mean age, percentage of male participants, number of patients taking ACEI and/or ARB, number of patients taking other antihypertensives or no treatment, type and dose of antihypertensive drug, number of patients experiencing the primary outcome in each treatment group as well as details for possible matched characteristics were recorded.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    2.1 Data source, search strategy and elegibility criteria: To identify publications regarding the clinical outcomes of COVID-19 in infected patients under treatment or not under treatment with ACEI/ARB, an extensive search of the literature was conducted in Medline (through PubMed interface), Cochrane Library, Google Scholar and the preprint servers for the health sciences MedRxiv and BioRxiv, from December 2019 to May, 2nd 2020.
    Medline
    suggested: (MEDLINE, RRID:SCR_002185)
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Cochrane Library
    suggested: (Cochrane Library, RRID:SCR_013000)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    BioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)
    All analyses were conducted using RevMan software version 5.3.
    RevMan
    suggested: (RevMan, RRID:SCR_003581)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Finally, our findings must be interpreted in the context of the meta-analysis limitations. First, we could not make a distinction between the effects of ACEI and ARB separately, since most studies evaluated the two drug classes together. Second, all the studies included in the meta-analysis were observational and some were preprints. We could not find any randomized clinical trials that already showed results addressing our research question. On the other hand, in planning future trials, randomizing subjects to discontinue drugs with proven benefits would probably raise ethical concerns. Third, most of the included observational studies were retrospective cohorts and potential selection bias of patients is an indisputable concern. Fourth, residual confounders may be present in these observational studies and, even when measured, many studies did not make adjustments for such potential confounders. It must be noted, however, that not adjusting for age and cardiovascular morbidities would shift the results towards a higher risk since these variables are positively associated with the use of ACEI/ARB and with COVID-19 poorer outcomes. In conclusion, large prospective studies are required to confirm our finding and to explore the mechanisms for a possible protective role of RAS inhibitors in the context of COVID-19. In the meantime, these early results suggest that patients on ACEI/ARB should continue their treatment during COVID-19 illness, supporting current recommendations fro...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.05.19.20106799 on medRxiv